Rabies is the 10th most lethal infectious diseases in the world, causing approximately 60,000 deaths annually. Rabies is invariably fatal once symptoms occur. Prevention is the key in rabies control. In the US, rabies remains a significant wildlife- management and public-health challenge. The Centers for Disease Control and Prevention (CDC) report that over 90% of rabies cases in the United States are caused by wildlife. The economic burden of rabies in the US exceeds $300 million per year. Oral vaccination is the only effective way to control rabies in wildlife. The only licensed vaccinia-based oral rabies vaccine has cost-effectiveness and safety concerns. There is a need for safer and less expensive oral rabies vaccine both domestically and internationally. Here we propose to develop an oral rabies vaccine in rice grain using our proprietary protein expression technology. We think favorable safety profile, low production costs and high level expression of antigen of our expression system will make a safer vaccine at an affordable cost. In the present SBIR feasibility study, Ventria Bioscience and CDC will collaborate to develop four recombinant plasmid constructs of rabies virus glycoprotein genes. Using the constructed genes, we will develop transgenic rice plants to obtain transgenic seeds. After confirmed by viral glycoprotein expression analysis, devitalized transgenic rice grain will be fed in a mouse model to test oral immune responses and its protection in rabies challenge. We expect at least 1 of the 4 transgenic rice lines will generate at least 80% of protection in the mouse model. PUBLIC HEALTH RELEVANCE: Current oral rabies vaccine has limitation of both safety concern and high cost. We propose to produce the vaccine in rice grain which is safe and can be produced economically. The vaccine, upon meeting all production, quality, and regulatory requirements, would be used in baits for state and federal rabies prevention programs.